Post on 01-Jan-2016
description
Respiratory infectionsAtypical pathogens in community
acquired pneumoniaand Whooping cough
Natalie Neu, MD
Respiratory tract anatomy
Community acquired pneumonia(CAP)
and Atypical pathogens
• CAP-<50% of cases have identifiable cause
• Atypical- differ from classic symptoms of pneumococcal pneumonia and clinical picture different, more indolent, longer duration and may involve upper and lower respiratory tract
• Atypicals usually don’t respond to penicillin
Clinical scenario 1
• Myra is a 21 year old medical student living in the dorm room studying for exams
• She goes to student health complaining of low grade fever, headache, non-productive cough, sore throat and general malaise
• Her exam reveals mild fine inspiratory rales- nothing impressive
• The Dr sends her for an xray that reveals bilateral infiltrates
Mycoplasma
• Does not have a cell wall
• Cell membrane contains sterols not present in other bacteria
• Special enriched media needed for growth
• Laboratory cultures rarely done- diagnosis usually by serology (IgG)
• Bedside test- cold agglutinins
Mycoplasma- pathogenesis and immunity
• P1- protein attachment factor- facilitates attachment to sialic acid receptors of respiratory epithelium and RBC surface
• Remains extracellular• Causes local destruction of cilia, interferes with
normal airway clearance which leads to mechanical irritation and persistent cough
• Acts as a super antigen stimulating PNM’s and macrophages to release cytokines (TNF, IL1, and IL 6)
Walking pneumonia
• Lacks seasonal pattern, spread by droplet secretions
• Common in children and young adults• Mild respiratory symptoms• Complications: otitis media, erythema
mulitforms, hemolytic anemia, myocarditis, pericarditis, neurologic abnormalities
• Treatment: erythromycin
Erythema multiforme
Clinical scenario 2
• JM 10 week old infant born to a 16 year old mom• Pregnancy history limited due to lack of prenatal
care but baby born full term, no complications, left hospital 2 days
• Seen by pediatrician at 2 weeks old with eye discharge was given eye drops
• Returned to ER: RR 60, cough but no fever• Xray done and bloods drawn
Chlamydia trachomatis xray
Chlamydial pneumonias: trachomatis, pneumoniae, psittaci
• Intracellular parasites- use host high energy phosphate compounds
• Trilaminar outer membrane which contains LPS
• Two phase life cycle- Elementary body (infectious) and reticulate body (divides by binary fission in the host)
Chlamydial pneumonias
• Infect non-ciliated columnar cells
• Multiply in alveolar macrophages
• Perivascular and peribronchiolar infiltrates
• Clinical symptoms due to host immune response
• Immunity not long-lasting
• Diagnosis by serology- four fold rise in titer
C. trachomatis pneumonia
• Neonatal infection presents at 1-3 months of age• Staccato-like cough, rapid respiratory rate• NO FEVER• Evaluation: minimal chest findings, xray
hyperinflation and diffuse infiltrates, peripheral eosinophilia
• Associations: atherosclerotic heart disease• Treatment: erythromycin• Prevention: maternal screening
C. pneumoniae
• Single strain- TWAR • Prolong incubation period• Common in school age children• Indolent course-sore throat, chronic cough, no
fever• Chest xray variable (lobar, diffuse, bilateral)• Diagnosis: PCR and serology• Treatment: macrolide, doxycycline, levofloxacin
C. psittaci
• History: Parrot exposure• Mild clinical respiratory symptoms, fever, rash• Concomitant symptoms: cns- headache, confusion,
cranial nerve palsy, seizures; hepatitis; pericarditis• Xray-consolidation, reticular nodular pattern,
adenopathy• Titers: > 1:64 diagnostic• Treatment: doxy, tetracycline, erythromycin
Clinical scenario 3
• Charlie is a 68 year old retired plumber who recently underwent a renal transplantation
• Felt great and was tinkering around his house updating his bathroom fixtures
• Came for follow up visit complaining of high fever, cough, chills and his wife said that he was acting confused at times
• Laboratory studies reveal WBC 35,000 with left shift, LDH >1000
• Chest xray reveals multilobar process
Legionella species
The 1976 Legionnaire’s Convention, Philadelphia, PA
• 29/180 patients died due to pneumonia• Identification of a gram negative bacilli• Epidemiologic link to being in the lobby of
Hotel A; historical link to 1966 outbreak in a psychiatric hospital
• National panic- worries about biologic and chemical warfare- media frenzy
• 6 months to identify the organism
Legionella pneumophila and micdadei
• 2-6% community acquired pneumonias• Risk: immunocompromised, hospitalized, and
outbreak situations• Gram negative bacilli- don’t stain with common
reagents• Fastidious and grow on supplemented media• Organisms contaminate water sources: air
conditioning systems and water tanks
Legionella: pathogenesis and immunity
• Intracellular pathogen- multiply in macrophages and monocytes
• Proteolytic enzymes kill the infected respiratory cells leading to formation of microabscesses
• Immunity- Cell mediated immunity (T cells) needed for immune response
Legionnaires disease
• Incubation period up to 10 days• Clinical- influenza like illness or severe
manifestation= pneumonia• Fever (105), rigors, cough, headache• Multilobular infiltrates and microabscesses• Extrapulmonary manifestations: CNS, diarrhea,
abdominal pain, nausea• High white counts, abnormal liver, renal panel• High mortality-15-20% depending on host
Legionella: Diagnosis, prevention and treatment
• Urine antigen detection assays- EIA for L.pneumophila only
• Serology >1:128 positive however late development of antibodies
• Culture on special media• Treatment: macrolide or levofloxacin• Prevention: hyperclorination, super heating,
continuous copper-silver ionization
Clinical scenario 4(Loyola Univ Medical Center)
• Jerry, a 7 month old child, comes to clinic with a running nose, sneezing and slightly irritable
• Diagnosed with URI • Returns 2 weeks later because he is turning blue
with coughing spells. Spells are worse at night, seems to have spasms and then he “whoops” for air.
• Examination reveals mildly dehydrated, not distressed, clear lung exam
• WBC reveals leucocytosis with lymphocytosis
Bordetella pertussis
Bordetella pertussis“Whooping cough”
• Fastidious, gram negative coccobacilii
• Pertussis, parapertussis, and bronchiseptica
• Spread by respiratory droplets
• Rapid multiplication in mucus membrane
• No bacteremia
• Toxins cause local tissue damage
Binding and uptake by phagocytic cells
Pertussis toxin
Toxin production and disease manifestation
G protein and ADP riboyslation
Pertussis
• Incidence declined due to vaccine• Affects children under 1 and adults with waning
immunity• Incubation period 7-10 days• Three stages of disease: catarrhal, paroxysmal,
convalescent• Diagnosis: special media- Bordet-Gengou- blood,
charcoal, and starch. Nasopharyngeal culture• Serologic testing: acute and convalescent titers
Toxins and pathogenesisPertussis toxin- increased CAMP
Increased resp secretions and mucus (paroxysmal stage)
Adenylate cyclase and hemolysin toxin
Inhibit leukocyte chemotaxis, phagocytosis, and killing
Heat-labile toxin Local tissue destruction
Tracheal cytotoxin Destroys ciliated epith cells, IL-1 (fever), NO (kills epithelial cells)
Lipid A and Lipid X Activate alternative complement, cytokine release
Pertussis clinical symptoms